Questions & Answers About Cardiac Arrest Research

Questions and Answers for the ROC Cardiac Studies

 What is ROC?

ROC stands for Resuscitation Outcomes Consortium. ROC was created to study which treatments help people with out-of-hospital cardiac arrest or severe traumatic injury.

The mission of the Resuscitation Consortium is to provide infrastructure and project support for clinical trials and other outcome-oriented research in the areas of cardiac arrest and severe traumatic injury that will rapidly lead to evidence-based change in clinical practice. ROC Investigators conduct collaborative trials of variable size and duration (equally directed towards the cardiac and trauma populations), leveraging the combined power of the member institutions and promoting the rapid translation of promising scientific and clinical advances for the public good. 

ROC consists of 10 locations across the US and Canada, and involves more than 20,000 fire and emergency medical service (EMS) providers who serve a combined population of nearly 15 million people from diverse urban, suburban and rural regions.

 

Continuous Cardiac Compressions Study (CCC)

 

What is the purpose of this study?

The primary aim of the trial is to compare survival at hospital discharge after continuous chest compressions (CCC) versus standard American Heart Association-recommended cardiopulmonary resuscitation with interrupted chest compressions (ICC) in patients with out-of-hospital cardiac arrest.  A cardiac arrest is a life-threatening medical emergency where the heart stops beating. Individuals experiencing a cardiac arrest lose blood flow to the brain and become unconscious. Without treatments such as CPR (pushing on the chest with the heels of the hands to help the blood move, and helping a person breathe), and an electric shock to restore the heartbeat, death can begin in 4-6

minutes. It is estimated that more than 95% of cardiac arrest victims die before reaching a hospital.  Because survival is so poor, doctors are trying to find better treatments to save more lives. For this study, CCC consists of a series of three cycles of continuous chest compressions without pauses for ventilation followed by rhythm analysis, until restoration of spontaneous circulation or completion of the three cycles of CPR whichever occurs first. ICC consists of series of 3 cycles of standard CPR, each cycle comprised of sets of 30 chest compressions with interposed ventilations at a compression:ventilation ratio of 30:2 (per AHA guidelines) followed by rhythm analysis until ROSC or three cycles of CPR whichever occurs first. Other aims of the trial include comparison of neurological status at discharge and adverse events between control and intervention groups. 

Fire and EMS agencies are randomized to one of the two treatments described above, and the agencies will crossover to the opposite treatment arms approximately every 6 months throughout the study.

 

How many patients will be enrolled in the study?

Approximately 23,600 patients will be enrolled at all of the ROC regions in the United States and Canada.

When will the study start?

The first patient is was enrolled in the summer of 2011. The start time will be different at each of the ROC sites depending on when they receive local approval to begin the study.

 

How long will it take to complete the study?

The study is expected to last approximately 3 years.

 

Where will the trial be conducted?

The CCC trial will be done at 8 locations across the US and Canada. Almost 125 fire and EMS organizations, involving more than 20,000 fire and emergency medical service (EMS) providers who serve a combined population of nearly 15 million people from diverse urban, suburban and rural regions will participate in the study.

 

How do patients enroll in the study?

Patients in the CCC study have experienced a cardiac arrest. Cardiac arrests occur unexpectedly and because of the inability to predict when a cardiac arrest is going to occur, a person cannot sign up ahead of time. Patients are unconscious when they are enrolled in CCC and unable to discuss their treatment. Life-supporting interventions must be given immediately in the field to try to save their life.

 

How can research be done on a person without the person’s permission?

There are serious medical situations where a patient is unconscious so they are unable to give permission to be enrolled in a study. Cardiac arrest is one of those situations. The CCC study will be conducted under federal regulations that allow an exception of informed consent.

Amiodarone, Lidocaine, Placebo or neither Study (ALPS)

 

What is the purpose of this study?

The goal of ALPS is to determine if survival to hospital discharge after an out-of-hospital cardiac arrest is improved with early (and if necessary) repeated therapeutic administration of a new Captisol-Enabled formulation of IV amiodarone (PM101) compared to no antiarrhythmic drug (placebo) or lidocaine. A cardiac arrest is a life-threatening medical emergency where the heart stops beating.  Individuals experiencing a cardiac arrest lose blood flow to the brain and become unconscious.  Without treatments such as CPR (pushing on the chest with the heels of the hands to help the blood move, and helping a person breathe), and an electric shock to restore the heartbeat, death can begin in 4-6 minutes. It is estimated that more than 95% of cardiac arrest victims die before reaching a hospital. Because survival is so poor, doctors are trying to find better treatments to save more lives.

ALPS will compare the benefit of what is believed (but as yet unproven) to be the most effective antiarrhythmic drug (amiodarone) against the traditional standard drug (lidocaine) and against neither (placebo) in shock-resistant cardiac arrest. As such, it will potentially answer two critical questions: (1) are antiarrhythmic drugs effective for the treatment of VF cardiac arrest? (2) is amiodarone preferable to lidocaine for such treatment? Answering these questions will determine the proven role (if any) of antiarrhythmic drugs for future generations of patients with out-of-hospital cardiac arrest.

Patient who meet the study inclusion criteria are randomized (1:1:1/a process like a coin toss) to receive amiodarone, lidocaine or neither medication (a placebo made up of salt water), in addition to all other standard treatment measures for cardiac arrest given by the EMS. Patients receive standard medical care when admitted to the hospital.

 

Why is a placebo included in one of the randomization arms?

Antiarrhythmic medications (amiodarone, lidocaine) are frequently used as part of advanced care to treat ventricular arrhythmias (irregular heart rhythms) that persist or recur during a cardiac arrest.  Although much is known about the pharmacological effects of these drugs, there is a considerable gap in knowledge between our understanding of their mechanisms of action and whether their use actually improves survival after cardiac arrest. No pharmacologic agent has ever been demonstrated to improve survival to hospital discharge after cardiac arrest. It is not known whether these drugs may cause more harm than good.

 

Where will the study be conducted?

The study will be done at 10 locations across the U.S. and Canada. Almost 70 EMS organizations, involving more than 10,000 EMS providers who serve a combined population of nearly 15 million people from diverse urban, suburban and rural regions will participate in the ROC Continuous Cardiac Compressions study.

 

How many patients will be enrolled in the study?

Approximately 3,000 patients will be enrolled at all of the ROC regions in the United States and Canada.

 

When will the study start?

The first patient is expected to be enrolled in early 2012. The start time will be different at each of the ROC sites depending on when they receive local approval to begin the study.

How long will it take to complete the study?

The study is expected to last approximately 3 years.

How do patients enroll in the study?

Patients in ALPS have had a cardiac arrest. Cardiac arrests occur unexpectedly and because of the inability to predict when a cardiac arrest is going to occur, a person cannot sign up ahead of time.  Patients are unconscious when they are enrolled in CCC and unable to discuss their treatment. Life supporting interventions must be given immediately in the field to try to save their life.

 

How can research be done on a person without the person’s permission?

There are serious medical situations where a patient is unconscious so they are unable to give permission to be enrolled in a study. Cardiac arrest is one of those situations. The ALPS study will be conducted under federal regulations that allow an exception from informed consent.

 

What is exception from informed consent for emergency research?

In 1996, the FDA developed specific regulations to permit research without prospective consent under carefully controlled circumstances. This is in recognition of the unique kind of emergency medical situations in which patients or family members cannot give informed consent before treatment as well as the need to allow emergency care to advance through research.

According to FDA regulations, to qualify for an exception from informed consent, the research study must involve participants suffering from a life-threatening disease process or injury for which the current standard of care is associated with a very high failure or mortality rate. In addition, there must be reasonable evidence that the research has the potential to provide real and direct benefit to the patient. Furthermore, studies must be held to the highest ethical standards. The ROC studies have undergone many independent rigorous reviews to ensure that they meet these standards.

The use of a randomized clinical trial is the “gold standard” for determining what works best for people.  For treatments that must be given immediately to be effective, exception from informed consent research is considered appropriate by federal regulatory bodies and many ethicists who study this field. The obligation to improve standard treatments that yield poor results in life-threatening conditions is also considered an ethical imperative, as is maintaining individual rights of citizens. In exception from consent trials, citizens receive standard treatment in addition to research treatment.  To be tested in this fashion, the research treatment has to have shown promise in earlier or smaller studies.

 

If a family member is present when the patient has a cardiac arrest, why is the family not asked for permission?

In order to give permission to participate in a study, it is important that the person giving permission understands what is being said to them, and can make a well-informed decision.  Family members are usually very upset during a medical emergency and are not able to concentrate or comprehend what is being said during the emergency. Cardiac arrest is an extreme emergency during which the patient will die within a few minutes if treatment is not begun immediately. Patients in cardiac arrest are unconscious and unable to discuss their treatment, and any time taken to discuss

their treatment with family robs the patient of immediately starting life-saving measures.

 

Are there any risks to the patient?

Patient safety is carefully monitored and recorded for any complications of study treatments. As is possible with any new treatment, there are risks involved. Possible reactions to the study drugs are seizures, a severe drug allergy, or a slow heart beat that may require a pacemaker (a small device placed under the skin to speed up the heart beat). Patients may also experience a reaction to the drug that causes redness, warmth, tenderness or a hard swelling under the skin where the drug entered the body. These are the same risks that would be associated with the use of these drugs during cardiac arrest under other circumstances (outside the trial), and are another justification for including placebo (that is, using neither drug) in the trial. That is, if these drugs are not effective and have the potential risk of adverse side effects, avoiding their use entirely may actually prove to be the preferred treatment

Also, there are risks associated with traditional CPR done by emergency medical providers. These risks include possible rib fractures, pneumothorax (collapse of part of the lung), laceration of the liver (internal cut of liver) or abdominal injury or pulmonary edema (fluid in the lungs). However the patient would have experienced these risks regardless of whether they were enrolled in this research.

 

Can patients be enrolled in both the ALPS and CCC study?

Patients can be enrolled in both studies. The majority of patients will be enrolled in the CCC study, and about 20-25% will be enrolled in ALPS.